Related Experiment Video
Updated: Jul 16, 2026
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
White Matter Anomaly Associated Cognitive Impairment During Systemic Inflammation Is Related to CX3CR1 Mediated
Xue Shi1, Jingdong Zhang1,2,3, Huangying Zhao3
1Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Background:
The effects of CX3CR1 and CCR2 deficiency on cognition are related to microglia-neuron interactions and synaptic plasticity in the hippocampus. Contact between microglia and Ranvier's nodes has been identified in the brain white matter (WM). We propose that WM anomaly associated cognitive impairment during systemic inflammation is due to the alteration of microglia-node interactions, which impacts the conductive function of axons.
Methods:
Novel object recognition and Y-maze tests were performed, and the corpus callosum (CC) axon compound action potential (CAP), microglia proportional area, density of microglia-node contact, and infiltrated circulating immune cells were examined in wild-type (WT), CX3CR1, and CCR2 knockout mice before and after systemic lipopolysaccharide (LPS) administration.
Results:
CX3CR1 deficiency significantly reduced rate of exploring new objects and new paths, decreased CC CAP and microglia-node contact compared with WT mice. CX3CR1 or CCR2 knockout diminished the microglial proportional area. Systemic LPS significantly increased microglial proportional area and immune cell infiltration but decreased time and rate of exploring new objects and new paths, declined CAP, and reduced microglia-node contact in CX3CR1 expressed mice. The absence of CX3CR1 in normal conditions deteriorated cognitive performance and CC WM tract conductive function and reduced microglia density and microglia-node contact chance. However, defects in cognitive performance and CC WM tract conductivity, and disruption of microglia-node contact by systemic LPS were protected by CX3CR1 knockout.
Conclusion:
CX3CR1 is involved in modulating CC WM microglia-node contact, maintaining the CC WM tract conductive function, and improving cognitive performance. In the context of systemic LPS and associated neuroinflammation, CX3CR1 seems to dominate the disruption of microglia-node communication and CC WM tract conductive function, consequently causing cognitive problem. This may be achieved primarily through CX3CR1 mediated microglia activities and activation and subordinately via the infiltration of CX3CR1high circulating immune cells into the CC WM tract.
Insights
CX3CR1 deficiency impairs cognitive function and white matter conductivity by altering microglia-node interactions. However, CX3CR1 knockout protects against LPS-induced neuroinflammation and cognitive deficits.
Area of Science:
- Neuroscience
- Immunology
- Cognitive Science
Background:
- Microglia-neuron interactions and synaptic plasticity in the hippocampus influence cognition.
- Microglia contact with Ranvier's nodes in brain white matter (WM) is crucial.
- WM anomalies and systemic inflammation can cause cognitive impairment by altering microglia-node interactions and axonal conductivity.
Purpose of the Study:
- To investigate the role of CX3CR1 and CCR2 in cognitive function and white matter integrity.
- To examine the impact of systemic inflammation on microglia-node interactions and cognitive performance.
- To elucidate the mechanisms underlying neuroinflammation-induced cognitive deficits.
Main Methods:
- Novel object recognition and Y-maze tests were used to assess cognitive performance.
- Corpus callosum (CC) axon compound action potential (CAP) measured white matter conductivity.
- Microglia characteristics, microglia-node contact, and immune cell infiltration were analyzed in wild-type (WT) and knockout mice before and after lipopolysaccharide (LPS) administration.
Main Results:
- CX3CR1 deficiency reduced cognitive exploration, CC CAP, and microglia-node contact.
- Systemic LPS increased microglial area and immune cell infiltration, while decreasing cognitive performance, CC CAP, and microglia-node contact.
- CX3CR1 knockout protected against LPS-induced cognitive and conductivity deficits, and disruption of microglia-node contact.
Conclusions:
- CX3CR1 modulates CC WM microglia-node contact, white matter conductivity, and cognitive performance.
- During neuroinflammation, CX3CR1 appears to mediate the disruption of microglia-node communication and WM conductivity, leading to cognitive problems.
- These effects are primarily driven by CX3CR1-mediated microglial activation and secondarily by the infiltration of CX3CR1-expressing immune cells.
More Related Videos
Related Concept Videos
01:22Gut-Brain Axis
01:26Bacterial Meningitis II: Pathophysiology